It is generally assumed that the functions of the immune system decline with advancing age, resulting in a higher susceptibility to infectious disease. This is also the case for humoral immunity, with decreased antibody (Ab) production and shortened duration of Ab production following vaccination. There are many potential factors involved with the observed immune senescence of the elderly including; underlying health or disease manifestations, nutritional status, or aberrant immunological parameters such as the presence of relatively large T cell clonal expansions (TCE). Recent studies suggest that the presence of TCE in aged individuals is associated with a decreased ability to mount an effective Ab response. To better understand the potential link between TCE and decreased immune status, we have employed a non-human primate (NHP) model of aging in which we will compare antigen-specific humoral immune responses in rhesus macaques (RM) at >18 years of age (old) separated into groups that either have pre-existing TCE or do not present with TCE at the time of vaccination. The immune responses of these two elderly groups will then be compared to the results obtained following vaccination of young adult controls. Our primary goal is to determine the effects of aging on humoral immunity in RM, an excellent model of human aging. Our secondary goal is to decipher the clinical relevance (if any) of peripheral TCE on antigen-specific humoral immune responses following vaccination. To that effect, we will determine the effect of aging (+/-TCE) on: 1) the induction of antigen-specific antibody production 2) the maintenance and quality of antigen-specific antibody production, and 3) the magnitude, phenotype, and longevity of the antigen-specific memory B cell compartment. The results of these studies will be important for determining if TCE represent an important underlying mechanism of immune senescence and/or if they will be useful as a biomarker of immune dysfunction in aged individuals. A better understanding of these factors will pave the way towards more effective vaccination strategies for immunizing vulnerable elderly populations.